Showing papers on "Alkylation published in 2012"

Nonnatural Amino Acid Synthesis by Using Carbon–Hydrogen Bond Functionalization Methodology

Abstract: During the last years, transition-metal-catalyzed carbon-hydrogen bond functionalization has witnessed an explosive growth.[1] The use of C-H bond as a functional group is appealing because of shortening of reaction pathways and simplification of retrosynthetic analyses. However, most of the reports that deal with carbon-hydrogen bond conversion to carbon-carbon bonds involve either methodology development or mechanistic investigations. The applications in synthesis of natural products or their analogues are rare.[2] The limited use may be explained by the following issues. First, methods that result in functionalization of alkane C-H bonds are relatively rare.[3] Second, harsh reaction conditions are typically used that may be incompatible with sensitive functionalities. Third, methods often lack generality and require non-removable directing groups. We have reported the β-arylation of carboxylic acid and γ-arylation of amine derivatives by employing an 8-aminoquinoline or picolinic acid auxiliary, catalytic Pd(OAc)2, and an aryl iodide coupling partner (Scheme 1).[4a] Subsequently, several other auxiliaries were investigated for carboxylic acid β-arylation.[4b] Use of 2-thiomethylaniline auxiliary affords selective monoarylation of methyl groups. In contrast, use of 8-aminoquinoline auxiliary allows either diarylation of methyl or monoarylation of methylene groups. The arylation regioselectivity is determined by formation of double five-membered chelate 1. Scheme 1 Auxiliaries for C-H Bond Arylation Several other groups have recently used these directing groups in synthesis of natural products.[5] Corey has used the 8-aminoquinoline auxiliary to arylate sp3 C-H bonds in amino acid derivatives.[5a] However, monoarylation of alanine derivatives was not demonstrated and stereochemical integrity of arylation products as well as directing group removal was not reported. Developing new methodology for unnatural amino acid synthesis is important since they are used in drug discovery, protein engineering, peptidomimetics, glycopeptide synthesis, and click chemistry in biologically relevant systems.[6–7] Methods for preparation of chiral nonracemic unnatural α-amino acids involve synthesis of racemates followed by resolution, use of chiral auxiliaries, asymmetric hydrogenation, and biological approaches.[8] A general method for unnatural amino acid synthesis from chiral pool would expand the toolbox that is available for their preparation. We report here a method of palladium-catalyzed synthesis of protected unnatural amino acids by C-H bond functionalization that employs readily available starting materials derived from chiral pool. The functionalizaton of amino acid C-H bonds requires installation of a directing group and protection of the amino group. Phthaloyl group was chosen for protection of the amino functionality.[9] Directing group was installed by reacting phthaloylamino acid chlorides[10] with 8-aminoquinoline or 2-thiomethylaniline. N-Phthaloylalanine derivative 2 was arylated by PhI in the presence of a palladium catalyst and base. Subsequently, directing group was removed by treatment with BF3*Et2O in methanol at 100 °C (Table 1).[11] Nearly identical enantiomeric excess of 4 was observed by employing AgOAc, AgOCOCF3, or CsOAc bases at 60–70 °C (entries 3–8). Higher reaction temperatures resulted in erosion of product enantiomeric excess (entries 1, 4, 9), as did addition of pivalic acid (entry 2). The optimal combination of yield and enantiomeric excess was obtained by employing palladium acetate catalyst in combination with AgOAc at 60 °C (entry 5). Table 1 Reaction Optimization. Use of 2-thiomethylaniline derivative allows for a selective monoarylation of methyl group in 2 (Scheme 2). Arylation of 2 by iodobenzene affords 3 in 78% yield. 4-Methoxyiodobenzene is reactive and the arylation product 5 was isolated in 68% yield. 2-Iodonaphthalene and 2-iodobenzothiophene afforded the products in good yields. β-(2-Naphthyl)alanine-containing peptides are highly specific Pin1 inhibitors.[12] Interestingly, 3-iodo-1-methylindole can be coupled with 2 to give an N-methylated tryptophan derivative 8 in 61% yield. An azido functionality is tolerated and 3-azidophenylalanine derivative 9 was obtained in 81% yield. Thus, a wide variety of substituted phenylalanines can be made from a readily available, single starting material 2 in a convergent fashion. Two of the arylated derivatives were subjected to cleavage of directing group. N-Phthaloylphenylalanine methyl ester 4 was obtained in 87% yield and 90% ee. The benzothiophene derivative 10 was obtained in 80% yield. Scheme 2 Synthesis of Modified Phenylalanine Derivatives. 8-Aminoquinoline directing group can be used for diarylation of methyl and monoarylation of methylene functionalities (Scheme 3). Diarylation of 11 was accomplished by 3,4-dimethyl-1-iodobenzene and 4-iodobenzoic acid ethyl ester and the products 12 and 13 were isolated in excellent yields. Interestingly, arylation of methylene groups occurs with high diastereoselectivity favoring the anti diastereomers. Protected phenylalanine can be arylated by 4-iodoanisole to give 91% of the product 14 with crude diastereomer ratio 24:1. Similarly, arylation by 2-iodothiophene results in formation of a single diastereomer 15 in 95% yield. Protected lysine can be arylated by 4-iodoanisole and 2-iodothiophene in high yields and diastereoselectivities. Arylation of a leucine derivative affords products 18 and 19 in high yields. The reactions were typically run on a 0.5 mmol scale. A 5.55 mmol scale p-methoxyphenylation of the leucine derivative afforded 18 in 67% yield. Cleavage of directing group was investigated for 12 and 18. Methyl esters 20 and 21 were obtained in 80 and 58% yields, respectively. Compound 21 was produced in 86% ee that could be upgraded to 95% ee (85% recovery) by one recrystallization. Additionally, relative stereochemistry of 21, which is a derivative of highly constrained β-isopropyltyrosine,[13] was verified by X-ray crystallography. Scheme 3 Aminoquinoline Auxiliary. Preliminary results in alkylation and acetoxylation of amino acid C-H bonds are reported in Scheme 4. Thus, alanine derivative 11 was alkylated by 1-iodooctane affording 22 in 42% yield. Compound 22 is a derivative of a lipidic amino acid which has shown tumor cell growth inhibitor activity.[14] Acetoxylation of 23 gave 24 in 53% yield.[15–16] Scheme 4 Alkylation and Acetoxylation. The arylation diastereoselectivity is set either at the C-H activation or, less likely, at reductive elimination step.[17] The H/D exchange in 23 was examined by heating the substrate with catalytic Pd(OAc)2 in CD3CO2D-toluene-d8 mixture. (Scheme 5). After 5 hours at 100 °C, 64% of deuterium incorporation was observed at 3S position with minimal (<10%) incorporation at 3R position. A generalized reaction mechanism can be proposed. Formation of a palladium amide 23a is followed by the C-H activation that affords 23b. The complex 23b then can be protonated or deuterated leading to 25. Since protonation likely occurs with retention of configuration,[18] it can be assumed that 23b has a trans arrangement of phthaloyl and phenyl groups and that the diastereoselectivity of the arylation is set at the stage of palladation. Oxidative addition to give a high-valent[19] Pd intermediate 26 is followed by reductive elimination that proceeds with retention of configuration. Oxidative addition of aryl iodides to palladium(II) may be facilitated by the silver salts since they are known to complex aryl iodides.[20] Ligand exchange affords 27 and regenerates 23a. Scheme 5 Mechanistic Considerations. In conclusion, we have shown that synthesis of a number of substituted phenylalanine derivatives is possible by using C-H bond functionalization methodology. The syntheses are highly convergent and employ N-phthaloylalanine possessing a 2-thiomethylaniline directing group. The use of 8-aminoquinoline directing group allows for the diarylation of methyl and diastereoselective monoarylation of amino acid methylene groups. Acetoxylation and alkylation of amino acid derivative C-H bonds is also possible.

Pd(II)-Catalyzed Regioselective 2-Alkylation of Indoles via a Norbornene-Mediated C–H Activation: Mechanism and Applications

Abstract: A palladium-catalyzed direct 2-alkylation reaction of free N-H indoles was developed based on a norbornene-mediated regioselective cascade C–H activation. The detailed reaction mechanism was investigated by NMR spectroscopic analyses, characterization of the key intermediate, deuterium labeling experiments, and kinetic studies. The results indicate that a catalytic cycle operates, in which an N-norbornene type palladacycle is formed as the key intermediate. Oxidative addition of alkyl bromide to the Pd(II) center in this intermediate is the rate-determining step of the reaction. The synthetic utility of this indole 2-alkylation method was demonstrated by its application in natural product total synthesis. A new and general strategy to synthesize Aspidosperma alkaloids was established employing the indole 2-alkylation reaction as the key step, and two structurally different Aspidosperma alkaloids, aspidospermidine and goniomitine, were synthesized in concise routes.

Replacing Conventional Carbon Nucleophiles with Electrophiles: Nickel-Catalyzed Reductive Alkylation of Aryl Bromides and Chlorides

Abstract: A general method is presented for the synthesis of alkylated arenes by the chemoselective combination of two electrophilic carbons. Under the optimized conditions, a variety of aryl and vinyl bromides are reductively coupled with alkyl bromides in high yields. Under similar conditions, activated aryl chlorides can also be coupled with bromoalkanes. The protocols are highly functional-group tolerant (−OH, −NHTs, −OAc, −OTs, −OTf, −COMe, −NHBoc, −NHCbz, −CN, −SO2Me), and the reactions are assembled on the benchtop with no special precautions to exclude air or moisture. The reaction displays different chemoselectivity than conventional cross-coupling reactions, such as the Suzuki–Miyaura, Stille, and Hiyama–Denmark reactions. Substrates bearing both an electrophilic and nucleophilic carbon result in selective coupling at the electrophilic carbon (R–X) and no reaction at the nucleophilic carbon (R–[M]) for organoboron (−Bpin), organotin (−SnMe3), and organosilicon (−SiMe2OH) containing organic halides (X–R–[M...

Production of high quality diesel from cellulose and hemicellulose by the Sylvan process: catalysts and process variables

Abstract: The Sylvan (2-methylfuran) diesel process involves the conversion of pentose biopolymers into premium diesel via furfural, by means of hydroxyalkylation/alkylation and hydrodeoxygenation reactions. In the hydroxyalkylation/alkylation step two Sylvan molecules are reacted with an aldehyde or a ketone to yield C12+ oxygenated intermediate molecules. Thus, the manuscript describes first the performance of the hydroxyalkylation/alkylation step with different soluble and solid catalysts, and among solids delaminated zeolites were identified as promising catalysts. The scope of the process has also been studied by reacting Sylvan with different aldehyde and ketone molecules. It has been found that for the one-step trimerization of Sylvan, sulfuric acid appears the most adequate catalyst and can be reused. The final hydrodeoxygenation step is studied in detail starting with C14 intermediates generated from two Sylvan and one butanal molecules as well as with the product generated by direct trimerization of Sylvan to yield the final corresponding mono-branched paraffinic diesel product. The Sylvan diesel process is an environmentally friendly process able to produce a high yield (87%) of a premium diesel with a cetane number of >70 and upper pour point of −75 °C from non-food biomass.

Copper-catalyzed di- and trifluoromethylation of α,β-unsaturated carboxylic acids: a protocol for vinylic fluoroalkylations.

Abstract: Dual action: the Lewis acid CuF(2) ⋅2 H(2)O efficiently catalyzes the reaction between electrophilic fluoroalkylating agents and α,β-unsaturated carboxylic acids by dually activating both reactants, thus affording di- and trifluoromethyl alkenes in high yields with excellent E/Z selectivity.

Nickel‐ and Cobalt‐Catalyzed Direct Alkylation of Azoles with N‐Tosylhydrazones Bearing Unactivated Alkyl Groups

Abstract: The functionalization of heteroaromatic compounds has received much attention from synthetic chemists because heteroaromatic cores are ubiquitously found in pharmaceuticals, biologically active compounds, and functional materials. The transition-metal-catalyzed cross-coupling reaction of heteroaryl halides or organometallic compounds is a powerful and reliable strategy to obtain functionalized heteroaromatic compounds. On the other hand, recent advances in the metal-mediated C H functionalization provide a complementary and potentially more efficient methodology to heteroaromatic compounds, because additional preactivation steps, such as the halogenation or stoichiometric metalation of the parent heterocycles, to prepare the coupling reagents can be avoided. Direct arylation, alkenylation, and alkynylation have been widely explored. However, the alkylation reaction is relatively challenging, 5] despite the fact that alkyl chains attached to aromatic nuclei are known to generally enhance lipophilicity and solubility, and to tune the aromatic p-stacking and p-conjugation of the corresponding oligomers and polymers. In particular, direct introduction of secondary alkyl side chains into heteroarenes remains elusive, probably because of the difficulty in controlling an undesired b-H elimination of an alkyl metal intermediate. A few successful examples with alkyl halides are still restricted in substrate scope to cyclic frameworks, such as cyclohexane and cyclopentane. A metal-catalyzed C H insertion approach with alkenes, and a copper-catalyzed alkylation with N-tosylhydrazones, which has very recently been reported by Wang and co-workers (see below), appear to be good alternatives, however, these processes are limited to activated systems, thus only enabling benzylation and allylation. Therefore, further developments for more general alkylation methodologies are strongly desired. Herein, we report nickeland cobalt-based catalysts for the direct alkylation of azoles with N-tosylhydrazones. The catalytic systems are compatible with various unactivated secondary alkyl groups, including cyclic and even more challenging acyclic alkyl groups. Our working hypothesis is inspired by our previous success in the nickel-catalyzed direct alkylation of azoles with primary alkyl halides and recent developments in the use of N-tosylhydrazones in cross-coupling reactions (Scheme 1). An initial base-assisted direct nickelation of a heteroarene provides a heteroaryl nickel species A. On the

Replacing conventional carbon nucleophiles with electrophiles: nickel-catalyzed reductive alkylation of aryl bromides and chlorides

Abstract: A general method is presented for the synthesis of alkylated arenes by the chemoselective combination of two electrophilic carbons Under the optimized conditions, a variety of aryl and vinyl bromides are reductively coupled with alkyl bromides in high yields Under similar conditions, activated aryl chlorides can also be coupled with bromoalkanes The protocols are highly functional-group tolerant (−OH, −NHTs, −OAc, −OTs, −OTf, −COMe, −NHBoc, −NHCbz, −CN, −SO2Me), and the reactions are assembled on the benchtop with no special precautions to exclude air or moisture The reaction displays different chemoselectivity than conventional cross-coupling reactions, such as the Suzuki–Miyaura, Stille, and Hiyama–Denmark reactions Substrates bearing both an electrophilic and nucleophilic carbon result in selective coupling at the electrophilic carbon (R–X) and no reaction at the nucleophilic carbon (R–[M]) for organoboron (−Bpin), organotin (−SnMe3), and organosilicon (−SiMe2OH) containing organic halides (X–R–[M

Ir(I)-catalyzed C-H bond alkylation of C2-position of indole with alkenes: selective synthesis of linear or branched 2-alkylindoles.

Abstract: A cationic iridium-catalyzed C2-alkylation of N-substituted indole derivatives with various alkenes has been developed, which selectively gives linear or branched 2-alkylindoles in high to excellent selectivity. This protocol relies on the use of the carbonyl group on the nitrogen atom of indole as a directing group: a linear product was predominant when an acetyl group was used as a directing group, and a branched product was predominant with a benzoyl group.

Dehydrative C–H Alkylation and Alkenylation of Phenols with Alcohols: Expedient Synthesis for Substituted Phenols and Benzofurans

Abstract: A well-defined cationic Ru–H complex catalyzes the dehydrative C–H alkylation reaction of phenols with alcohols to form ortho-substituted phenol products. Benzofuran derivatives are efficiently synthesized from the dehydrative C–H alkenylation and annulation reaction of phenols with 1,2-diols. The catalytic C–H coupling method employs cheaply available phenols and alcohols, exhibits a broad substrate scope, tolerates carbonyl and amine functional groups, and liberates water as the only byproduct.

Regioselective, borinic acid-catalyzed monoacylation, sulfonylation and alkylation of diols and carbohydrates: expansion of substrate scope and mechanistic studies.

Abstract: Synthetic and mechanistic aspects of the diarylborinic acid-catalyzed regioselective monofunctionalization of 1,2- and 1,3-diols are presented. Diarylborinic acid catalysis is shown to be an efficient and general method for monotosylation of pyranoside derivatives bearing three secondary hydroxyl groups (7 examples, 88% average yield). In addition, the scope of the selective acylation, sulfonylation, and alkylation is extended to 1,2- and 1,3-diols not derived from carbohydrates (28 examples); the efficiency, generality, and operational simplicity of this method are competitive with those of state-of-the-art protocols including the broadly applied organotin-catalyzed or -mediated reactions. Mechanistic details of the organoboron-catalyzed processes are explored using competition experiments, kinetics, and catalyst structure-activity relationships. These experiments are consistent with a mechanism in which a tetracoordinate borinate complex reacts with the electrophilic species in the turnover-limiting step of the catalytic cycle.

Direct C-H functionalization of enamides and enecarbamates by using visible-light photoredox catalysis.

Abstract: Direct C-H functionalization of various enamides and enecarbamates was realized through visible-light photoredox catalyzed reactions. Under the optimized conditions using [Ir(ppy)(2)(dtbbpy)PF(6)] as photocatalyst in combination with Na(2)HPO(4), enamides such as N-vinylpyrrolidinone could be easily functionalized by irradiation of the reaction mixture overnight in acetonitrile with visible light. The scope of the reaction with respect to enamide and enecarbamate substrates by using diethyl 2-bromomalonate for the alkylation reaction was explored, followed by an investigation of the scope of alkylating reagents used to react with the enamides and enecarbamates. The results indicated that reaction takes place with quite broad substrate scope, however, tertiary enamides with an internal C=C double bond in the E configuration could not be alkylated. Alkylation of N-vinyl tertiary enamides and enecarbamates gave monoalkylated products exclusively in the E configuration. Alkylation of N-vinyl secondary enamides gave doubly alkylated products. Double bond migration was observed in the reaction of electron-deficient bromides such as 3-bromoacetyl acetate with N-vinylpyrrolidinone. A mechanism is proposed for the reaction that is different from reported reactions of SOMOphiles with a nonfunctionalized C=C double bond. Further tests on the trifluoromethylation and arylation of enamides and enecarbamates under similar conditions showed that the reactions could serve as a mild, practical, and environmentally friendly approach to various functionalized enamides and enecarbamates.

Deoxygenative reduction of carbon dioxide to methane, toluene, and diphenylmethane with [Et2Al]+ as catalyst.

Abstract: The strong Lewis acid [Et(2)Al](+) catalyzes the reduction of carbon dioxide with hydrosilanes under mild conditions to methane. In benzene solution, the side products toluene and diphenylmethane are also obtained through Lewis acid catalyzed benzene alkylation by reaction intermediates.

A highly active bifunctional iridium complex with an alcohol/alkoxide-tethered N-heterocyclic carbene for alkylation of amines with alcohols.

Abstract: A series of new iridium(III) complexes containing bidentate N-heterocyclic carbenes (NHC) functionalized with an alcohol or ether group (NHC?OR, R=H, Me) were prepared. The complexes catalyzed the ...

The Direct Asymmetric α Alkylation of Ketones by Brønsted Acid Catalysis

Abstract: The development of new catalytic asymmetric methodologies for organic transformations is an important area of research for organic chemists. Among the numerous organic reactions, a alkylation of carbonyl compounds is a highly valuable C C bond-formation strategy. In the last ten years, a number of organocatalytic methods, including asymmetric phase-transfer catalysis and asymmetric amino catalysis, have been developed for the a alkylation of carbonyl compounds. Alcohols are ideal alkylation reagents for this reaction because water is the sole by-product. 4a–g] Theoretically, Brønsted acids are good catalysts for promoting the a alkylation of carbonyl compounds, especially ketones and aldehydes, with alcohols. The reasons for this include the following: 1) Brønsted acids can promote enol formation with the ketones or aldehydes; 2) Brønsted acids can activate alcohols by protonating the hydroxy group, and then promote formation of an active carbocation intermediate; and 3) whereas amino catalysts are potentially alkylated by the alkylation reagent and then deactivated, Brønsted acids are not. Despite their advantages, Brønsted acids have not been used for asymmetric catalysis in this important C C bondformation reaction, 8] and only a few direct alkylation reactions of carbonyl compounds with alcohols catalyzed by achiral Brønsted acids have been described. Our group reported an asymmetric Brønsted acid catalyzed a alkylation reaction in 2009, but this involved enamides, preactivated ketones, as donors. As a continuation of this research, we have attempted direct asymmetric a alkylation of ketones with alcohols by Brønsted acid catalysis, and herein we report the first example of such an alkylation of unmodified ketones with alcohols in high yields (up to 98%) with high diastereoselectivities (d.r., up to 99:1), and high enantioselectivities [up to 97 % enantiomeric excess (ee)]. Recently, 3-indolylmethanols were extensively used in the alkylation reaction of carbonyl compounds through organocatalysis. 10] However, our initial attempt to introduce the 3-indolylmethanol 1a (Figure 1) for the direct alkylation of unmodified ketones was unsuccessful. We found that 1a decomposed quickly when it was mixed with cyclohexanone and a Brønsted acid catalyst in an organic solvent (see the Supporting Information). It is well known that 1a can produce the stable carbocation or vinylogous imino intermediate A under acidic conditions (Figure 1), and we speculated that the weak electrophilicity of A could lead to the poor results in the direct alkylation of ketones. According to Mayr et al. , ketones have lower nucleophilicity (N) than enamides. Consequently, the electrophilicity (E) of the corresponding electrophiles should be increased. Because positive charge density has a large influence on electrophilicity, we chose to introduce an electron-withdrawing group on 3-indolylmethanol 1a to increase the electrophilicity of intermediate A. The isatin-derived 3-hydroxy-3-indolyoxindole 2 a could serve as a good alkylation reagent for the direct alkylation reaction. Compound 2a can lead to the intermediate B, which has similar stability to A, under acidic conditions. In addition, the amide group of intermediate B increases the positive charge density on C3, thus making it more electrophilic than intermediate A. Therefore, the reaction of 2a with ketones could generate chiral 3-indolyloxindoles, a novel type of indole and oxindole that could be potentially used in indole alkaloid synthesis. Thus, cyclohexanone (3a) and 3-hydroxy-3-indolyloxindole 2a were chosen as reactants for the present study (see Table 1). 1,1’Bi-2-napthol-derived phosphoric acids 4 were chosen as catalysts because they are powerful Brønsted acid catalysts that have been used in many organic transformations. After the selection of the compounds for the model reaction, 2a was reacted with 3a in toluene with 4 a as the catalyst. As expected, the reaction proceeded smoothly and the desired alkylation product 5 a was obtained in good yield with high diastereoselectivity and enantioselectivity (Table 1, entry 1). These promising results encouraged evaluation of the catalytic ability of other phosphoric acids (Figure 2). All of the catalysts were acidified before use (see the SupportFigure 1. Selection of the alkylation reagent in this work.

Multistep One‐Pot Synthesis of Enantioenriched Polysubstituted Cyclopenta[b]indoles

Abstract: Consecutive chiral thiourea catalyzed α-alkylation of an aldehyde with indolylmethanol derivatives, and two Broensted acid catalyzed Friedel—Crafts alkylation reactions with indoles at room temperature provide the title compounds in most cases as single diastereomers and with up to 99% enantioselectivity.

Direct Arylation/Alkylation/Magnesiation of Benzyl Alcohols in the Presence of Grignard Reagents via Ni-, Fe-, or Co-Catalyzed sp3 C–O Bond Activation

Abstract: Direct application of benzyl alcohols (or their magnesium salts) as electrophiles in various reactions with Grignard reagents has been developed via transition metal-catalyzed sp(3) C-O bond activation. Ni complex was found to be an efficient catalyst for the first direct cross coupling of benzyl alcohols with aryl/alkyl Grignard reagents, while Fe, Co, or Ni catalysts could promote the unprecedented conversion of benzyl alcohols to benzyl Grignard reagents in the presence of (n)hexylMgCl. These methods offer straightforward pathways to transform benzyl alcohols into a variety of functionalities.

Iridium-catalyzed oxidant-free dehydrogenative C-H bond functionalization: selective preparation of N-arylpiperidines through tandem hydrogen transfers.

Abstract: In addition to creating efficient and selective methodologies, the rise of green chemistry has led organic chemists and chemical industry to take into account the impact of these processes on the environment. Among the different ecofriendly approaches, homogeneous metal-catalyzed hydrogen autotransfers aimed at developing benign and atom-efficient protocols for the construction of carbon–heteroatom or carbon–carbon bonds have attracted considerable interest. In these reactions, the transient formation of unsaturated carbonyl or imine intermediates, arising from the dehydrogenation of alcohols or amines acting as alkylating reagents, has been successfully used for the preparation of a-alkylated carbonyl derivatives and amines accompanied by the formation of either water or valuable ammonia as the only side product. Owing to the potential of these transformations, recent developments have focused on the preparation of welldefined ruthenium and iridium complexes to allow more selective and milder reaction conditions, water soluble or reusable catalysts, and continuous flow approaches. In addition, the appealing amination from ammonia to afford alkylated amines has been reported by several groups. However, to date no tandem methodologies based on hydrogen autotransfer involving three different partners have been reported. Recently, we achieved the unprecedented oxidant-free dehydrogenation of cyclic N-benzyl and N-alkylamines using a ruthenium(II)–arene catalyst (A ; Scheme 1) featuring a phosphinesulfonate chelate. This reactivity involves hydrogen autotransfers and was successfully applied to the

Aqueous Phase Hydroalkylation and Hydrodeoxygenation of Phenol by Dual Functional Catalysts Comprised of Pd/C and H/La-BEA

Abstract: Aqueous phase catalytic phenol hydroalkylation and hydrodeoxygenation have been explored using Pd/C combined with zeolite H-BEA and La-BEA catalysts in the presence of H2. The individual steps of phenol hydrogenation, cyclohexanol dehydration, or alkylation with phenol were individually investigated to gain insight into the relative rates in the cascade reactions of phenol hydroalkylation. The hydroalkylation rate, determined by the concentrations of phenol and cyclohexanol in phenol hydroalkylation, required the hydrogenation rate to be relatively slow. The optimized H+/Pd ratio was 21, which allowed achieving comparable cyclohexanol formation rates via phenol hydrogenation and consumption rates from alkylation with phenol in phenol hydroalkylation. La-BEA was shown to be more selective for hydroalkylation than H-BEA in combination with Pd/C, because cyclohexanol dehydration was retarded selectively compared to alkylation of phenol. This indicates that dehydration is solely catalyzed by Bronsted acid sit...

Photoredox-initiated α-alkylation of imines through a three-component radical/cationic reaction.

Abstract: Key features of the approach are the wide substance scope, short reaction times, high atom-economy (no side products) and good to excellent chemical yields.

Regioselective CH Alkylation of Anisoles with Olefins Catalyzed by Cationic Half‐Sandwich Rare Earth Alkyl Complexes

Abstract: Anisole derivatives are important aromatic compounds, their structural motifs are observed in many useful materials, such as pharmaceuticals, natural products, and fluorescent dyes. The development of efficient, selective processes for the synthesis of anisole derivatives is therefore of much interest and importance. Among the most straightforward and atomeconomical routes to anisole derivatives is the C H alkylation of anisoles with alkenes. However, such C H bond alkylation approaches for the synthesis of anisole derivatives have met with limited success to date. The Friedel–Crafts reaction of anisoles with alkenes is a well-known route to alkylated anisole derivatives, but such Lewis acid catalyzed alkylation reactions generally suffer from poor regioselectivity and often give a mixture of orthoand para-regioisomers with the pararegioisomer as the main product, owing to steric and electronic influences. Recently, the late-transition-metalcatalyzed ortho-C H alkylations of various aromatic compounds possessing a directing group have been reported. However, these late-transition-metal catalysts seemed unsuitable for the ortho-selective C H alkylation of anisoles, because the interaction between an ether group and the metal center is too weak to regioselectively direct the C H bond activation. To the best of our knowledge, the catalytic ortho-selective C H alkylation of anisoles with an alkene has not been previously reported. In view of the strong oxophilicity of rare-earth metal ions and the high activity of rare-earth alkyl species toward unsaturated C C bonds, we envisioned that the rareearth alkyl complexes might serve as unique catalysts for the ortho-selective C H alkylation of anisoles with alkenes. Herein, we report the rare-earth catalyzed C H bond addition of anisoles to various olefins, which constitutes the first example of catalytic ortho-selective alkylation of an anisole compound with an alkene. We have recently found that the silylene-linked halfsandwich rare-earth alkyl complexes such as 1 (Figure 1) could serve as unique catalysts for the ortho-selective C H silylation of anisoles with hydrosilanes, because the coordination of the methoxy group to the rare-earth metal ion can direct the C H activation to selectively take place at the ortho-position. At first, we chose complex 1 as a catalyst to examine the reaction of anisole with styrene and ethylene, but no alkylation product was observed (See Table 1, entry 1). To

Mild Metal‐Free Tandem α‐Alkylation/Cyclization of N‐Benzyl Carbamates with Simple Olefins

Abstract: Easy does it! The chemoselective oxidative α-C(sp(3))-H alkylation/cyclization reaction of N-benzyl carbamates using simple mono-, di-, and trisubstituted olefins provides functionalized N-heterocycles such as oxazinones. A TEMPO oxoammonium salt serves as the oxidant, making it possible to carry out the reaction at low temperatures. Neither a metal catalyst nor preactivation in the α-position to the nitrogen group are needed.

Alkylation of Pyridone Derivatives By Nickel/Lewis Acid Catalysis

Abstract: The alkylation of a variety of pyridones and pyrimidones with unactivated olefins in the presence of a Ni(0)—NHC—Lewis acid cocatalyst system proceeds with high linear-to-branched selectivity and moderate to high regioselectivity (towards position 6 of pyridone).

The Iridium‐Catalyzed Synthesis of Symmetrically and Unsymmetrically Alkylated Diamines under Mild Reaction Conditions

Abstract: An iridium catalyst – stabilized by an anionic P,N ligand – was used for the symmetrical and unsymmetrical monoalkylation of para-, meta-, and ortho-benzenediamines. Benzyl and aliphatic alcohols were used as alkylating reagents. 28 derivatives were synthesized. 14 of them are new compounds. Furthermore, the alkylation of the pharmacological important diamine Dapson® (dapsone) is described. 14 dapsone derivatives were synthesized among them 9 new compounds.